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dc.contributor.authorFoster, Simon R
dc.contributor.authorBlank, Kristina
dc.contributor.authorHoe, Louise E See
dc.contributor.authorBehrens, Maik
dc.contributor.authorMeyerhof, Wolfgang
dc.contributor.authorPeart, Jason N
dc.contributor.authorThomas, Walter G
dc.date.accessioned2017-05-03T15:26:01Z
dc.date.available2017-05-03T15:26:01Z
dc.date.issued2014
dc.identifier.issn0892-6638
dc.identifier.doi10.1096/fj.14-256305
dc.identifier.urihttp://hdl.handle.net/10072/66477
dc.description.abstractG-protein-coupled receptors (GPCRs) are key mediators in cardiovascular physiology, yet frontline therapies for heart disease target only a small fraction of the cardiac GPCR repertoire. Moreover, there is emerging evidence that GPCRs implicated in taste (Tas1r and Tas2rs) have specific functions beyond the oral cavity. Our recent description of these receptors in heart tissue foreshadows a potential novel role in cardiac cells. In this study, we identified novel agonist ligands for cardiac-Tas2rs to enable the functional investigation of these receptors in heart tissue. Five Tas2rs cloned from heart tissue were screened against a panel of 102 natural or synthetic bitter compounds in a heterologous expression system. We identified agonists for Tas2r108, Tas2r137, and Tas2r143 that were then tested in Langendorff-perfused mouse hearts (from 8-wk-old male C57BL/6 mice). All Tas2r agonists tested exhibited concentration-dependent effects, with agonists for Tas2r108 and Tas2r137, leading to a ~40% decrease in left ventricular developed pressure and an increase in aortic pressure, respectively. These responses were abrogated in the presence of Gai and G߿ inhibitors (pertussis toxin and gallein). This study represents the first demonstration of profound Tas2r agonist-induced, G protein-dependent effects on mouse heart function.-Foster, S. R., Blank, K., See Hoe, L. E., Behrens, M., Meyerhof, W., Peart, J. N., Thomas, W. G. Bitter taste receptor agonists elicit G-protein-dependent negative inotropy in the murine heart.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.languageEnglish
dc.language.isoeng
dc.publisherFederation of American Societies for Experimental Biology
dc.publisher.placeUnited States
dc.relation.ispartofstudentpublicationN
dc.relation.ispartofpagefrom4497
dc.relation.ispartofpageto4508
dc.relation.ispartofissue10
dc.relation.ispartofjournalThe FASEB Journal
dc.relation.ispartofvolume28
dc.rights.retentionY
dc.subject.fieldofresearchBiochemistry and cell biology
dc.subject.fieldofresearchBiochemistry and cell biology not elsewhere classified
dc.subject.fieldofresearchZoology
dc.subject.fieldofresearchZoology not elsewhere classified
dc.subject.fieldofresearchMedical physiology
dc.subject.fieldofresearchMedical physiology not elsewhere classified
dc.subject.fieldofresearchcode3101
dc.subject.fieldofresearchcode310199
dc.subject.fieldofresearchcode3109
dc.subject.fieldofresearchcode310999
dc.subject.fieldofresearchcode3208
dc.subject.fieldofresearchcode320899
dc.titleBitter taste receptor agonists elicit G-protein-dependent negative inotropy in the murine heart
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.rights.copyrightSelf-archiving of the author-manuscript version is not yet supported by this journal. Please refer to the journal link for access to the definitive, published version or contact the author[s] for more information.
gro.hasfulltextNo Full Text
gro.griffith.authorPeart, Jason N.


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